Abstract Purpose: Activities of daily living require the sub-axial cervical spine (C2-C7) to have substantial mobility in flexion-extension, lateral bending and axial rotation. These segments also demonstrate a characteristic motion coupling between lateral bending and axial rotation. Cervical total disc replacement (TDR) has been clinically used to treat radiculopathy and myelopathy. The ability of the TDR to replicate physiologic motion is critical to protect adjacent levels from degeneration. Hypotheses: (H1) The ability of cervical TDR to restore physiologic primary and coupled motions and load distribution at the reconstructed segment would depend on the prosthesis design features. (H2) The ability of cervical TDR to restore physiologic quantity and quality of motions and load distribution at the reconstructed segment would depend on surgical techniques such as: (1) the width of the annular window made for implant insertion, (2) whether the PLL is preserved or resected, and (3) prosthesis position in the disc space. (H3) A second TDR at an adjacent level will not adversely affect the biomechanics of the index level TDR. Specific objectives: (1) Measure three-dimensional (3-D) intervertebral motion profiles and load sharing among the disc and facet joints in cervical spines under loads experienced during ADL for the following: (a) intact; (b) after C5-C6 TDR as a function of prosthesis design and surgical technique variability; and (c) after a second TDR at C6-C7. (2) Develop a new technique to generate specimen-specific, CT-based 3-D computer models to assess motions, gapping, and contact at the facet joints and uncovertebral joints in the intact segment and after TDR as a function of prosthesis design and variability in surgical implantation technique. Research Plan: This project will use a combination of experimental studies and CT-based specimen-specific modeling. Experimental Studies: The experiments will be performed using 60 fresh human cervical spine specimens of adult male and female donors <60 years of age. The specimens will be assigned to six prostheses groups (n=10 each) that fall into four design categories: (I) single spherical bearing design; (II) saddle-shaped bearing design; (III) mobile core design with two bearings; and (IV) six degrees-of-freedom compressible design. The surgical technique variables will include: (I) Implant position within the disc space (anterior vs. posterior); and (II) Integrity of the soft-tissue envelope at the implanted level including (a) the width of the window (narrow vs. wide) made in the anterior annulus for prosthesis insertion, and (b) the preservation or resection of posterior longitudinal ligament (intact vs. resected). CT-Based, Specimen-Specific Models: 3-D computer models of individual specimens (60 total) will be created from CT scans. Four aluminum markers implanted in each vertebra, visible on CT and included in the computer model, will be probed during the experiments to establish a 'digital link' between the specimen and its model. Experimental vertebral motion data will be used to 'drive' the computer model, producing validated measurements throughout the specimen's range of motion. The models will be used to assess facet joint and uncinate process articulations in terms of gap distances, relative localized motions, and contact areas. Statistical Analysis: Experimental data and model results will be analyzed using repeated-measures ANOVA with one factor (prosthesis design), and post hoc multiple comparisons. We estimate 10 specimens per prosthesis to give 80% statistical power in detecting a difference of at least 25% in the outcome measures. Significance: We propose to generate objective data on the abilities of cervical disc prostheses of different designs to restore physiologic cervical spine mechanics. In addition, we will develop an innovative technique to assess facet and uncovertebral joint motion in the intact segment and after implantation of disc prostheses using specimen-specific CT-based 3-D computer models. These findings can be immediately translated to clinical practice to improve the surgical treatment outcomes for painful degenerative disease of the cervical spine.